Thermophilic ligno-cellulolytic fungi: The future of efficient and rapid bio-waste management.

To accelerate the process of decomposition using consortia of thermophilic ligno-cellulolytic fungi, different crop residues viz. sorghum (SG), soybean (SS), maize (MS), sugarcane (SC), cotton (CS) and pigeon pea (PS) with a varied C:N ratio and sawdust (SD) having high lignin content were collected and used for decomposition process. Compost quality assessed by evaluating different maturity and stability indices at five succeeding stages [first mesophilic (M1), thermophilic (T), second mesophilic (M2), cooling (C) and humification (H)]. A significant reduction was observed in the C:N ratio, biodegradability index, nitrification index, ratio of water-soluble carbon to organic nitrogen (WSC/Org.N) with an increase in concomitant over time while Ash (%), organic matter loss (%), CEC/TOC ratio, cellulose biodegradation ratio (BR) and lignin/cellulose ratio were significantly increased with time. By correlation study, biodegradability index (BI) and fluorescein diacetate (FDA) hydrolysis emerged as the most suitable compost maturity and stability parameters, respectively. Principal component analysis (PCA) results confirmed that BI, BR, WSC/Org. N and FDA can be regarded as key indicators for assessing compost quality. Our findings conclude that fungal consortia of Tricoderma viride, Rhizomucor pusillus, Aspergillus awamori and Aspergillus flavus can accelerate decomposition time from 8 to 12 months (which is normal farming practice) to 120 days.

Long-term in situ moisture conservation in horti-pasture system improves biological health of degraded land.

In situ moisture conservation practices can conserve fertile topsoil and enhance available water in soil profile. We hypothesised that reclaiming degraded land ecologically through tree + pasture + in situ moisture conservation practices would significantly improve soil organic carbon (SOC) and health. Hence, the objectives were a) to identify changes in nutrient cycling enzymes and SOC status due to different in situ soil moisture conservation options in surface and subsurface soil layers, and b) to test the potentiality of soil enzymes to determine long-term nutrient availability. We conducted a long-term experiment involving aonla (Emblica officinalis) trees + pasture (Cenchrus ciliaris + Stylosanthes seabrana) + in situ soil moisture conservation measures viz. staggered contour trenches (T1), continuous contour trenches (T2), stone mulch (T3), vegetative barriers (T4), control (T5) and fallow land (T6) since 2007. Recommended dose of nitrogen (N), phosphorus (P) and potassium (K) were added to all treatments, except T6. SOC concentration increased by ~51 and 31% in T1 and T2, respectively, over T5 in surface (0-15 cm) soil. Culturable bacterial and fungal populations increased by ~20 and 95% in T1 over T5 in surface soil. Activities of all soil enzymes increased in T1 and T2 (ranging from 42 to 289%) over T5 and T6 in both surface and sub-surface (15-30 cm) layers. However, specific activity of phenol oxidase was ~25% lower for T1 than T6, suggesting more efficient SOC sequestration in T1. Moreover, geometric mean enzyme activity of T1 was ~65 and 33% higher than T5 and T3, respectively, in surface soil. Treated soil quality index (T-SQI) of T1 was ~184% higher than T5. Soil functional diversity was also ~1.24 and 1.22 times higher in T1 and T2 than T5, respectively. Peroxidase was the major C degrading enzyme in this ecosystem. Protease, urease and phosphatase significantly influenced N and P availability along with fruit and pasture yields. Importantly, ~96, 62 and 82% variability of SOC, N and P concentrations, respectively, could be attributed to their corresponding enzyme activities. Principal components analysis (PCA) revealed one-way operational role of soil enzymes. Thus, enzymes are potentially important for recycling nutrients from litters, root biomass of fruit trees and grasses to boost their availability in the long run. Adoption of horti-pasture system combined with moisture conservation practices and staggered contour trenches or continuous contour trenches ensured higher above ground biomass yield, SOC, nutrient availability and soil quality. Thus, long-term use of these practices could be recommended for reclamation and improving soil health and crop productivity of degraded lands of central India.

Soil respiration, labile carbon pools, and enzyme activities as affected by tillage practices in a tropical rice-maize-cowpea cropping system.

In order to identify the viable option of tillage practices in rice-maize-cowpea cropping system that could cut down soil carbon dioxide (CO2) emission, sustain grain yield, and maintain better soil quality in tropical low land rice ecology soil respiration in terms of CO2 emission, labile carbon (C) pools, water-stable aggregate C fractions, and enzymatic activities were investigated in a sandy clay loam soil. Soil respiration is the major pathway of gaseous C efflux from terrestrial systems and acts as an important index of ecosystem functioning. The CO2-C emissions were quantified in between plants and rows throughout the year in rice-maize-cowpea cropping sequence both under conventional tillage (CT) and minimum tillage (MT) practices along with soil moisture and temperature. The CO2-C emissions, as a whole, were 24 % higher in between plants than in rows, and were in the range of 23.4-78.1, 37.1-128.1, and 28.6-101.2 mg m(-2) h(-1) under CT and 10.7-60.3, 17.3-99.1, and 17.2-79.1 mg m(-2) h(-1) under MT in rice, maize, and cowpea, respectively. The CO2-C emission was found highest under maize (44 %) followed by rice (33 %) and cowpea (23 %) irrespective of CT and MT practices. In CT system, the CO2-C emission increased significantly by 37.1 % with respect to MT on cumulative annual basis including fallow. The CO2-C emission per unit yield was at par in rice and cowpea signifying the beneficial effect of MT in maintaining soil quality and reduction of CO2 emission. The microbial biomass C (MBC), readily mineralizable C (RMC), water-soluble C (WSC), and permanganate-oxidizable C (PMOC) were 19.4, 20.4, 39.5, and 15.1 % higher under MT than CT. The C contents in soil aggregate fraction were significantly higher in MT than CT. Soil enzymatic activities like, dehydrogenase, fluorescein diacetate, and ß-glucosidase were significantly higher by 13.8, 15.4, and 27.4 % under MT compared to CT. The soil labile C pools, enzymatic activities, and heterotrophic microbial populations were in the order of maize > cowpea > rice, irrespective of the tillage treatments. Environmental sustainability point of view, minimum tillage practices in rice-maize-cowpea cropping system in tropical low land soil could be adopted to minimize CO2-C emission, sustain yield, and maintain soil health.

How to survive on Mediterranean coastal cliffs: tolerance to seawater in early life-cycle stages in Brassica incana Ten. (Brassicaceae).

Mediterranean coastal cliffs are reservoirs of plant biodiversity, hosting vulnerable plant species particularly exposed to the risk of local extinction due to extreme abiotic conditions and climate changes. Therefore, studies aiming to understand the tolerance of cliff plant species to abiotic stresses are important to predict their long-time persistence or to highlight inherent threats. We used an integrative approach including anatomical, physiological and phenotypic analyses on (a) seeds, (b) cotyledons of seedlings; and (c) young plants to assess whether the cliff species Brassica incana, can tolerate exposure to different seawater (SW: 25%, 50% and 100%) concentrations during the early stages of its life cycle. Seeds could germinate when exposed to up to 50% SW. Seeds did not germinate in 100% SW, but could resume germination after washing with freshwater. Seed germination rate also decreased with increasing SW concentration. Exposure to SW decreased stomatal size and stomatal index of cotyledons and caused long-lasting and severe damage to the photochemical reactions of photosynthesis. Photochemistry was also sensitive to SW in young plants, but the effect was lower than in cotyledons. This may involve a remodulation of chloroplast dimensions and activation of cellular metabolism. However, photochemical reactions limited photosynthesis at100% SW even after recovery from SW exposure. Our data show that B. incana has strong tolerance to seawater and shows clear signs of halophytic adaptation. Whilst seeds and juvenile plants are able to withstand SW, the seedling stage appears to be more sensitive.

A Study on the Incidence and Impact of Dysglycemia in Non-diabetic Sepsis Patients.

Context Dysglycemia is common in severe sepsis and is associated with a poor prognosis. There is a limited amount of research on stress-induced dysglycemia in non-diabetic sepsis patients. Aim This study aims to estimate the incidence of dysglycemia among non-diabetic patients presenting with sepsis at the Emergency Department and to determine its correlation with gender, age, APACHE II (Acute Physiology and Chronic Health Evaluation) scores, diagnosis, and duration of hospital stay. Materials and methods The study was conducted at a medical college hospital in Kochi from January 1, 2023, to December 31, 2023. A minimum sample size of 77 was derived after a pilot study, with a 95% confidence interval and 10% allowable error. A total of 100 non-diabetic sepsis patients meeting the inclusion and exclusion criteria were analyzed with regard to gender, age, diagnosis, glycemic status (hypo/hyper/normoglycemic), APACHE II scores, and hospital stay duration. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York) software. Categorical variables were expressed as frequency and percentage. Continuous variables were presented as mean ± SD (standard deviation) and median (Q1-Q3). To test the statistical significance of the association between the presence of various factors (gender, age, diagnosis) and dysglycemia, the chi-square test was used. To test the statistical significance of the difference in the mean age and APACHE II score values with dysglycemia, an independent sample t-test was used. To test the statistical significance of the difference in the median hospital stay with dysglycemia, the Whitney U test was used. Data were represented as mean ± SD, and a p-value of <0.05 was considered to be statistically significant. Results The incidence of dysglycemia in the inclusion group was 49% (hypoglycemia in 16% and hyperglycemia in 33% of cases), and it increased with age (p=0.002). The majority of the dysglycemic patients fell into the age group >40 years. Dysglycemia was 54.8% in pneumonia and 66.7% in gastrointestinal sepsis ( p=0.138). Dysglycemia increased with an increase in APACHE II scores (p=0.017). The median hospital stay was almost the same in both normoglycemics and dysglycemics. Conclusion Dysglycemia is a frequent complication in non-diabetic patients with sepsis. It increased with age and APACHE II score, but it does not prolong the duration of hospital stay, nor is it associated with the diagnosis.

Arthrobotrys oligospora-mediated biological control of diseases of tomato (Lycopersicon esculentum Mill.) caused by Meloidogyne incognita and Rhizoctonia solani.

AIMS: To study the biocontrol potential of nematode-trapping fungus Arthrobotrys oligospora in protecting tomato (Lycopersicon esculentum Mill.) against Meloidogyne incognita and Rhizoctonia solani under greenhouse and field conditions. METHODS AND RESULTS: Five isolates of the nematode-trapping fungus Arthrobotrys oligospora isolated from different parts of India were tested against Meloidogyne incognita and Rhizoctonia solani in tomato (Lycopersicon esculentum Mill.) plants grown under greenhouse and field conditions. Arthrobotrys oligospora-treated plants showed enhanced growth in terms of shoot and root length and biomass, chlorophyll and total phenolic content and high phenylalanine ammonia lyase activity in comparison with M. incognita- and R. solani-inoculated plants. Biochemical profiling when correlated with disease severity and intensity in A. oligospora-treated and untreated plants indicate that A. oligospora VNS-1 offered significant disease reduction in terms of number of root galls, seedling mortality, lesion length, disease index, better plant growth and fruit yield as compared to M. incognita- and R. solani-challenged plants. CONCLUSION: The result established that A. oligospora VNS-1 has the potential to provide bioprotection agents against M. incognita and R. solani. SIGNIFICANCE AND IMPACT OF THE STUDY: Arthrobotrys oligospora can be a better environment friendly option and can be incorporated in the integrated disease management module of crop protection. Application of A. oligospora not only helps in the control of nematodes but also increases plant growth and enhances nutritional value of tomato fruits. Thus, it proves to be an excellent biocontrol as well as plant growth promoting agent.

Influence of elevated carbon dioxide and temperature on belowground carbon allocation and enzyme activities in tropical flooded soil planted with rice.

Changes in the soil labile carbon fractions and soil biochemical properties to elevated carbon dioxide (CO2) and temperature reflect the changes in the functional capacity of soil ecosystems. The belowground root system and root-derived carbon products are the key factors for the rhizospheric carbon dynamics under elevated CO2 condition. However, the relationship between interactive effects of elevated CO2 and temperature on belowground soil carbon accrual is not very clear. To address this issue, a field experiment was laid out to study the changes of carbon allocation in tropical rice soil (Aeric Endoaquept) under elevated CO2 and elevated CO2 + elevated temperature conditions in open top chambers (OTCs). There were significant increase of root biomass by 39 and 44 % under elevated CO2 and elevated CO2 + temperature compared to ambient condition, respectively. A significant increase (55 %) of total organic carbon in the root exudates under elevated CO2 + temperature was noticed. Carbon dioxide enrichment associated with elevated temperature significantly increased soil labile carbon, microbial biomass carbon, and activities of carbon-transforming enzyme like ß-glucosidase. Highly significant correlations were noticed among the different soil enzymes and soil labile carbon fractions.

Death attitudes and volunteering motives of youth during the flood in Kerala, India.

Kerala had witnessed a massive disaster in the form of a flood in 2018. The collective efforts and contribution of the youth in rescuing and rehabilitation were notable. OBJECTIVES: The current investigation aims to gauge the connection between death attitudes, volunteering motives, and sociodemographic variables among youth in Kerala. METHOD: The 150 participants who had volunteered to offer help in flood relief camps and rehabilitation programs from 3 districts in Kerala were given Voluntary Function Inventory (Clary et al., 1998) and Death Attitude Profile-Revised (Wong et al., 1994). RESULTS & CONCLUSION: Results of the study suggest that neutral acceptance of death attitude is positively related to volunteering motives. Likewise, volunteering motives vary significantly according to gender, marital status, socioeconomic status, and health perception, while death attitude differs significantly based on religion. This study directly implies terror management theory, which states that when reminded of their mortality, people intensify the desire to express culturally prescribed prosocial attitudes and engage in more volunteering behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Crustal structure in the Campanian region (Southern Apennines, Italy) from potential field modelling.

We present a 3D model of the main crustal boundaries beneath the Campanian region and the onshore and offshore surrounding areas, based on high-resolution potential field data. Our main objective is the definition of the main structural interfaces in the whole Campanian region from gravity and magnetic data, thanks to their ability to define them on a regional and continuous way. The complex morphology of the Mesozoic carbonate platform, which is fundamental to constrain the top of geothermal reservoir, was reconstructed by inverting the vertical gradient of gravity. We assumed local information from seismic models and boreholes to improve the model. We modeled the deep crustal structures by spectral analysis of Bouguer gravity and magnetic data. The inferred depth estimates indicate a shallow crystalline basement below the Tyrrhenian crust and the Apulian foreland and a significant depression beneath the Bradanic foredeep. The map of the Moho boundary shows a NE-SE verging trough below the Southern Apennine chain and two pronounced uplifts beneath the foreland and the Tyrrhenian crust. We also estimated the depth to the magnetic bottom, showing a thick magnetic crust below the mountain chain and shallow depths where the crustal heat flow is high. The models were compared with seismic sections along selected profiles; a good agreement was observed, despite of some inherent lower resolution for the gravity modelling from spectral methods. The regional covering and the continuity of our estimated crustal interfaces make it a new and valid reference for further geological, geophysical and geothermal studies, especially in areas such as northern and eastern Campania, where there is an incomplete geophysical and geological information.

Radiation induced effects on viability and antioxidant enzymes of crustaceans from different habitats.

The paper describes differential tolerance of two fresh water crustaceans Mesocyclops hyalinus and Allodiaptomus satanus to 60Co gamma radiation. Mesocyclops hyalinus is dominant species at site 1, near a Thermal Power Plant at Kolaghat East Midnapore where fly ash deposition is a regular phenomenon. Allodiaptomus satanus is dominant species at site 2 at Kolkata, Ballygung where anthroponotic activities are more pronounced. M. hyalinus is naturally exposed to more stressful situation than A. satanus as revealed by comparing the hydrological parameters of the two habitats. Experimental exposure to ionizing radiation resulted in differential changes in viability morphology and antioxidant enzyme activities in the two selected species. Survival experiments showed greater tolerance of M. hyalinus compared to A. satanus up to 8Gy (absorbed dose) after which if showed drastic fail in survival. More pronounced morphological changes were observed in A. satanus as compared to that in M. hyalinus. The pattern of changes in antioxidant enzyme activity is distinctly opposite in the two radiation exposed species. While in M. hyalinus stimulation in activity of both CAT (excepting at 10Gy absorbed dose) and SOD was observed A. satanus showed decrease in activity of both the enzymes when compared to their unirradiated counterparts.

Crustal structure of Sicily from modelling of gravity and magnetic anomalies.

We aim at modeling the main crustal and thermal interfaces of Sicily (Italy), a key area for understanding the geological complexity at the collisional boundary between the African and European plates. To this end, we analyze the gravity and magnetic fields, integrated with information from well logs, geology, heat flow, and seismic data. In order to make the most accurate description of the crustal structure of the area, we modeled with different methodologies the carbonate and crystalline top surfaces, as well as the Moho and the Curie isotherm surface. The reconstruction of the carbonate platform is achieved using a nonlinear 3D method constrained by the available seismic and borehole data. The crystalline top, the Curie, and the Moho are instead estimated by spectral analysis of both gravity and magnetic data. The results show a complex carbonate basement and a deep crystalline crust in central Sicily, with a prominent uplift beneath the Hyblean Plateau. Maps of the Moho and the Curie isotherm surface define a variable thermal and structural setting of Sicily, with very thin crust in the southern and eastern sectors, where high heat flow is found, and deep and cold crust below the Caltanissetta Basin.

Restructuring the Cellular Responses: Connecting Microbial Intervention With Ecological Fitness and Adaptiveness to the Maize (Zea mays L.) Grown in Saline-Sodic Soil.

Salt stress hampers plant growth and development. It is now becoming one of the most important threats to agricultural productivity. Rhizosphere microorganisms play key roles in modulating cellular responses and enable plant tolerant to salt stress, but the detailed mechanisms of how this occurs need in-depth investigation. The present study elucidated that the microbe-mediated restructuring of the cellular responses leads to ecological fitness and adaptiveness to the maize (Zea mays L.) grown in saline-sodic soil. In the present study, effects of seed biopriming with B. safensis MF-01, B. altitudinis MF-15, and B. velezensis MF-08 singly and in consortium on different growth parameters were recorded. Soil biochemical and enzymatic analyses were performed. The activity and gene expression of High-Affinity K+ Transporter (ZmHKT-1), Sodium/Hydrogen exchanger 1 (zmNHX1), and antioxidant enzymes (ZmAPX1.2, ZmBADH-1, ZmCAT, ZmMPK5, ZmMPK7, and ZmCPK11) were studied. The expression of genes related to lateral root development (ZmHO-1, ZmGSL-1, and ZmGSL-3) and root architecture were also carried out. Seeds bioprimed with consortium of all three strains have been shown to confer increased seed germination (23.34-26.31%) and vigor indices (vigor index I: 38.71-53.68% and vigor index II: 74.11-82.43%) as compared to untreated control plant grown in saline-sodic soil at 30 days of sowing. Results indicated that plants treated with consortium of three strains induced early production of adventitious roots (tips: 4889.29, forks: 7951.57, and crossings: 2296.45) in maize compared to plants primed with single strains and untreated control (tips: 2019.25, forks: 3021.45, and crossings: 388.36), which was further confirmed by assessing the transcript level of ZmHO-1 (7.20 folds), ZmGSL-1 (4.50 folds), and ZmGSL-3 (12.00 folds) genes using the qPCR approach. The uptake and translocation of Na+, K+, and Ca2+ significantly varied in the plants treated with bioagents alone or in consortium. qRT-PCR analysis also revealed that the ZmHKT-1 and zmNHX1 expression levels varied significantly in the maize root upon inoculation and showed a 6- to 11-fold increase in the plants bioprimed with all the three strains in combination. Further, the activity and gene expression levels of antioxidant enzymes were significantly higher in the leaves of maize subjected seed biopriming with bioagents individually or in combination (3.50- to 12.00-fold). Our research indicated that ZmHKT-1 and zmNHX1 expression could effectively enhance salt tolerance by maintaining an optimal Na+/K+ balance and increasing the antioxidant activity that keeps reactive oxygen species at a low accumulation level. Interestingly, up-regulation of ZmHKT-1, NHX1, ZmHO-1, ZmGSL-1, and ZmGSL-3 and genes encoding antioxidants regulates the cellular responses that could effectively enhance the adaptiveness and ultimately leads to better plant growth and grain production in the maize crop grown in saline-sodic soil.

Saffman-Taylor instability for generalized Newtonian fluids.

We study theoretically the linear Saffman-Taylor instability for non-Newtonian fluids in a Hele-Shaw cell. After introducing the notion of generalized Newtonian fluid we calculate the associated Darcy's law. We derive the relation governing the growth rate of normal modes for a large class of non-Newtonian flows. For shear-thinning fluids at high shear rate our theory provides Darcy's laws free of the nonphysical divergences appearing in the classical approaches. We characterize fluids which develop instabilities faster than Newtonian fluids under the same hydrodynamical conditions. Another primary result that this paper provides is that for some shear-thickening fluids, all normal modes are stable.

Earthworm Grazed-Trichoderma harzianum Biofortified Spent Mushroom Substrates Modulate Accumulation of Natural Antioxidants and Bio-Fortification of Mineral Nutrients in Tomato.

The present investigation was aimed at evaluating the impact of earthworm grazed and Trichoderma harzianum biofortified spent mushroom substrate (SMS) on natural antioxidant and nutritional properties of tomato. Results of the investigation reveal that earthworm grazing and T. harzianum bio-fortification led to significant improvement in the physico-chemical properties of fresh SMS and its application increased the accumulation of natural antioxidants and mineral content in tomato as compared to either T. harzianum biofortified SMS or fresh SMS. In particular, the earthworm grazed, T. harzianum biofortified SMS (EGTHB-SMS) was found to inhibit lipid peroxidation and protein oxidation with significant increase in total polyphenol and flavonoid content in tomato. Further, it increased Fe2+/Fe3+ chelating activity, superoxide anion radical scavenging activity compared to other treatments. The results thus suggest an augmented elicitation of natural antioxidant properties in tomato treated with EGTHB-SMS, resulting in a higher radical scavenging activity, that is highly desirable for human health. In addition, the use of SMS to enhance the nutritional value of tomato fruits becomes an environment friendly approach in sustainable crop production.

Bio-protective microbial agents from rhizosphere eco-systems trigger plant defense responses provide protection against sheath blight disease in rice (Oryza sativa L.).

Sheath blight of rice (Oryza sativa L.) caused by Rhizoctonia solani is a major disease and attempts are being made to develop microbe based technologies for biocontrol of this pathogen. However, the mechanisms of biocontrol are not fully understood and still require indepth study in the backdrop of emerging concepts in biological systems. The present investigation was aimed at deciphering the mechanisms of biocontrol of sheath blight of rice employing Pseudomonas fluorescens and Trichoderma harzianum as model agents for biocontrol. Initially 25, 5 and 5 strains of P. fluorescens, T. viride and T. harzianum, respectively, were screened for their biocontrol potential. Out of which, six strains with higher value of percent inhibition of fungal mycelium in dual plate assay were selected. The role of P. fluorescens, T. viride and T. harzianum were investigated in induction and bioaccumulation of natural antioxidants, defence-related biomolecules and other changes in plant which lead not only to growth promotion but also protection from pathogenic stress conditions in rice. The two most promising strains, P. fluorescens PF-08 and T. harzianum UBSTH-501 selected on the basis of in planta evaluation, when applied individually or in combination, significantly enhanced the accumulation of defence-related biomolecules, enzymes and exhibited biocontrol potential against R. solani. A modified/newly developed delivery system was applied for the first time in the experiments involving inoculation of plants with both bioagents, viz. P. fluorescens PF-08 and T. harzianum UBSTH-501. Results suggested that application of P. fluorescens PF-08 and T. harzianum UBSTH-501 alone or in combination, not only helps in control of the disease but also increases plant growth along with reduction in application of toxic chemical pesticides.

Nonlinear dynamics of short traveling capillary-gravity waves.

We establish a Green-Nagdhi model equation for capillary-gravity waves in (2+1) dimensions. Through the derivation of an asymptotic equation governing short-wave dynamics, we show that this system possesses (1+1) traveling-wave solutions for almost all the values of the Bond number theta (the special case theta=1/3 is not studied). These waves become singular when their amplitude is larger than a threshold value, related to the velocity of the wave. The limit angle at the crest is then calculated. The stability of a wave train is also studied via a Benjamin-Feir modulational analysis.

A cyber medical center.

This paper describes the design and implementation of a Cyber Medical Center (CMC) using web technology. The intention is to overcome the inefficiency of the traditional filing system for patients' medical records, which are considered to be time and space consuming. Another objective is to enhance the interaction between the user - the patient in this case - and the medical center personnel - the doctors and staff. This task is achieved by developing a cyber medical center interfaced with the Internet to provide direct public access. The traditional filing system is replaced by a database system for maintaining the electronic medical records of all patients in the medical center. The doctors or staff can either view the medical records or update them through the Intranet/Internet. This system has been successfully developed, implemented and tested on the Intranet platform. It will be available in a university medical center for practical use.

Allogeneic marrow transplantation for thalassemia.

Thirteen patients with homozygous beta thalassemia underwent allogeneic marrow transplantation from sibling donors, 12 of whom were heterozygous for beta thalassemia. Six patients were transplanted in an advanced stage of their disease while seven were transplanted early in their disease course. Donors and recipients were genotypically identical for the HLA-A, -B and -D loci in 11 cases and mismatched for the D locus in two. A variety of preparative regimens was utilized involving high doses of busulphan (Bu) and/or cyclophosphamide (CY) and/or total body irradiation (TBI). Failure of engraftment or autologous hematologic recovery after transient engraftment was seen after intensive preparative regimens including: CY 200 mg/kg and 800 rad of TBI; Bu 8 mg/kg and CY 200 mg/kg; and Bu 8 mg/kg, CY 200 mg/kg, and 300 rad of TBI. A regimen of Bu 16 mg/kg, CY 200 mg/kg, and 400 rad of TBI resulted in deaths from transplant-related causes in the three patients treated with this regimen. Seven of the 13 patients are surviving 363-665 days after transplant. Five of the seven failed to achieve engraftment or had autologous reconstitution after transient engraftment. Five of the six deaths were transplant related, and one patient died of cardiac failure one year after an unsuccessful transplant attempt. Two patients are surviving with engraftment and without thalassemia major 363 and 491 days after transplantation. Both of these patients were transplanted early in their disease course.

Potent tetracyclic guanine inhibitors of PDE1 and PDE5 cyclic guanosine monophosphate phosphodiesterases with oral antihypertensive activity.

Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).